RE1-silencing transcription factor (REST) network mRNAs (REST network mRNAs)

The RE1-silencing transcription factor (REST) network mRNAs comprise the set of messenger RNAs whose transcription is controlled by the REST protein, also known as the Neuron-Restrictive Silencer Factor (NRSF). REST acts as a master repressor by binding to the Repressor Element 1 (RE1) motif in the promoters of over 2,000 genes, many of which are essential for neuronal function, synaptic plasticity, and neurogenesis (Ooi & Wood, 2007, PubMed: 15685173). In healthy individuals, REST is highly expressed in non-neuronal cells to silence neuronal genes and is downregulated in mature neurons; however, its dysregulation is a hallmark of several pathologies. For example, the loss of REST in the aging brain is strongly linked to the progression of Alzheimer's disease and neurodegeneration, as REST normally provides neuroprotection against oxidative stress and amyloid-beta toxicity (Lu et al., 2014, PubMed: 24646994). Conversely, REST overexpression is observed in various cancers, where it can act as either an oncogene or a tumor suppressor depending on the cellular context (Negrini et al., 2013, PubMed: 22864569). Therapeutic targeting of this network typically involves small molecules or antisense oligonucleotides designed to modulate REST activity, thereby restoring the homeostatic balance of its downstream mRNAs to treat neurological disorders or malignancy.

Other names

NRSF network mRNAsNeuron-restrictive silencer factor network mRNAsRE1-containing gene transcriptsREST-regulated transcriptomeX-linked repressor element-1 silencing transcription factor network

Modulation of REST-mediated transcriptional repression through inhibition of REST protein activity or its recruitment of co-repressor complexes (e.g., HDACs, LSD1), thereby altering the expression levels of downstream network mRNAs (Soldati et al., 2012, PubMed: 22383400).